This project will address the problem of narcolepsy by conducting research on an animal model of the illness. The model consists of Doberman pinschers in which the sleep disorder is genetically transmitted by an autosomal recessive gene. Preliminary neurochemical evidence supports the hypothesis that a neurochemical defect is involved. We will pursue further elucidation of the pathological mechanisms in canine narcolepsy by carrying out studies in three areas. We will conduct regional assays of biogenic amines and their metabolites as well as measurement of binding sites and binding properties of dopaminergic, cholinergic, serotonergic, and adrenergic receptors. Other neurochemical studies will involve push-pull cannula approaches with assay of neurotransmitters and metabolites in perfusage. We also propose functional neuroanatomical mapping of cataplexy and REM sleep by 2-deoxyglucose techniques. Finally, we will investigate the neurophysiological substrates of narcolepsy be recording discharge patterns of single units in specific brainstem areas related to REM sleep control.